The goals of this research in synthetic organic and bioorganic chemistry are to synthesize natural antibiotics of the ionophore and macrolide classes and to design, synthesize, and study biomimetic hybrid molecules Incorporating macrocyclic hydropyran oligolides. Specific objectives are described below: 1 . Synthesis of 'second generation' macrocyclic hydropyran oligolides with directed functionality for the study of fundamental complexation, aggregation, and ion transport phenomena, including: (a) designed, structurally well-defined templates for assembling and characterizing amphiphilic helical peptide bundles as biomimetic transmembrane ion channels; (b) a conformationally favorable host for the water dimer, with potential as a self-assembling subunit in an extended, tubular supramolecular array; (c) other templates with self-complementary functionality for 'strict' (reversible) self-assembly into tubular supramolecules bound by ion pair or H-bonding interactions; (d) an ordered template Incorporating imidazole and sulfhydryl moieties to study two modes of self-assembly under physiological conditions, with potential application as a chiral proteinase mimic. 2. Total synthesis of the natural ionophore griseochelin (zincophorin), featuring: (a) a triply convergent route requiring only 19 linear steps for 17 stereogenic (13 asymmetric) centers; (b) direct comparison of anomeric radical and anionic hydropyran-to-vinylsulfone couplings in the context of acyclic stereocontrol. 3. Completion of a novel approach to polypropionate macrolides, exemplified by erythronolide B and erythronolide A, featuring: (a) exploitation of pseudosymmetrical C2->C6 and C8->C12 regions via a bis(dihydropyran) template; (b) double dioxanone-to-dihydropyran rearrangement to establish intact Cl->C13 array; (c) simultaneous multiple hydroborations to introduce several asymmetric centers at once; (d) a novel tactic for conformational restriction of the seco acid as an entropic aid to macrolactonization.